Transcription factor 7-like 2 (TCF7L2) polymorphism and context-specific risk of type 2 diabetes in African American and Caucasian adults: the Atherosclerosis Risk in Communities study.
OBJECTIVE
Although variants in the transcription factor 7-like 2 (TCF7L2) gene are consistently associated with type 2 diabetes, large population-based studies of African Americans are lacking. Moreover, few studies have investigated the effects of TCF7L2 on type 2 diabetes in the context of metabolic risk factors of type 2 diabetes.


METHODS
We investigated the association between the TCF7L2 rs7903146 polymorphism and type 2 diabetes in 2,727 African American and 9,302 Caucasian participants without diabetes who were inducted into the Atherosclerosis Risk in Communities study in 1987-1989 and followed for 9 years.


RESULTS
A total of 485 and 923 cases of type 2 diabetes were identified in African Americans and Caucasians, respectively. Compared with homozygous CC individuals, heterozygous CT and homozygous TT individuals had higher cumulative incidence of type 2 diabetes over 9 years of follow-up: 11.3% (95% CI 10.2-12.4) vs. 21.1% (20.8-21.4) and 27.9% (19.3-36.5) in African Americans, respectively, and 9.7% (8.8-10.6) vs. 11.3% (10.2-12.4) and 13.6% (11.1-16.1), respectively, in Caucasians. Individuals with the risk allele had the highest hazards of diabetes if they were obese and had low HDL cholesterol, followed by individuals with any one and none of the traits.


CONCLUSIONS
Our study provides the first significant evidence of association between the TCF7L2 rs7903146 polymorphism and type 2 diabetes risk in a large African American population and also demonstrates that the diabetes risk conveyed by the rs7903146 risk allele is substantially increased in the context of some metabolic risk factors for type 2 diabetes. Our study findings need to be replicated in other large, population-based studies.
Yan
Yu
Y
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
North
Kari E
KE
Ballantyne
Christie M
CM
Brancati
Frederick L
FL
Chambless
Lloyd E
LE
Franceschini
Nora
N
Heiss
Gerardo
G
Kottgen
Anna
A
Pankow
James S
JS
Selvin
Elizabeth
E
West
Suzanne L
SL
Boerwinkle
Eric
E
D001741:Black or African American / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics*
D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein